Coccidioidomycosis, also known as San Joaquin Valley Fever, is a fungal disease caused by Coccidioides immitis that is endemic in portions of Southern Arizona, central California, southern New Mexico and west Texas. The migration of not only permanent residents, but also agricultural workers to these areas increases exposure to C. immitis spores that lie dormant in the soil, and as the soil is turned, the spores become airborne and are inhaled. Once in the lungs, the arthroconidia transform into spherules. An acute respiratory infection occurs between seven days to three weeks after exposure and often resolves rapidly. However, in a significant number of cases, chronic pulmonary conditions or dissemination to the meninges, bones, and joints can result, leading to acute, life-threatening disease. Migrant laborers who are exposed to C. immitis are a highly mobile and underrepresented population, and unfortunately, this disease goes largely unacknowledged in the medical community. A variety of approaches have been used to fight coccidioidomycosis, including soil treatments, but only a vaccine can completely eliminate this "emerging disease." Currently, there are a number of C. immitis vaccine efforts that use a variety of approaches including selected recombinantly-expressed antigens. Our long-term goal is to develop a safe and effective vaccine against C. immitis. In this SBIR Phase I proposal, we will collaborate with Dr. Garry T. Cole, Dr. John Galgiani, Dr. David A. Stevens, and Dr. R. Duke of Globelmmune, Inc., and use Globelmmune's novel, proprietary recombinant yeast delivery system and test heat-killed yeast cells expressing C. immitis proteins as vaccine candidates. We will accomplish this in two specific aims: Aim One: Engineer yeast cells to express three C. immitis antigens using recombinant DNA technology. Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of C. immitis. This work will be a prelude to work in Phase II that will include detailed testing for in vivo efficacy and safety of each vaccine candidate in several C. immitis infection models. Ultimately, the Phase I and subsequent Phase II/III research will lead to the development of a vaccine against C. immitis.